Gancao Xiexin Decoction Ameliorates Ulcerative Colitis in Mice via Modulating Gut Microbiota and Metabolites.

Purpose: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that starts with mucosal inflammation of the rectum and extends proximally in the colon in a continuous manner over a variable distance. Although it is more common in North America and Western Europe, its incidence is also increasing in Asia. Despite the introduction of several different classes of medications, the treatment options for UC may be insufficiently effective and burdened with significant side effects. In the present study, the therapeutic effects of Gancao Xiexin decoction (GCXX) were investigated on mice with dextran sulfate sodium (DSS)-induced colitis with exploration of the underlying mechanisms. Methods: Colitis was induced in C57BL/6 mice by administering 3% DSS in drinking water for 7 days. GCXX and (or) the standard of care anti-inflammatory drug, mesalazine (5-aminosalicylic acid) were then administered for 7 days. The gut microbiota was characterized by 16S rDNA high-throughput gene sequencing and gut metabolites were detected by untargeted metabolomics. Germ-free mice were subsequently used to determine whether GCXX ameliorated UC principally through modulation of the gut microbiota. Results: GCXX treatment was demonstrated to significantly reduce disease activity index (DAI) scores, prevent colonic shortening, ameliorate colonic tissue damage and reduce the levels of pro-inflammatory cytokines. Furthermore, analysis of the gut microbiota showed that GCXX-treated mice had higher relative quantity of Dubosiella (P<0.05) and lower relative quantity of Escherichia-Shigella (P<0.05). Metabolomics analysis indicated that GCXX could reduce the level of linoleic acid (P<0.05) and regulate its metabolism pathway. Moreover, in germ-free mice, GCXX failed to increase body weight, reduce DAI scores, or alleviate either colonic shortening or colonic damage. Conclusion: The present study demonstrated that GCXX ameliorated DSS-induced colitis principally through modulating the gut microbiota and metabolites. This information should be integrated into the overall mechanisms of GCXX treatment of UC.

Administration of Lactobacillus reuteri Combined with Clostridium butyricum Attenuates Cisplatin-Induced Renal Damage by Gut Microbiota Reconstitution, Increasing Butyric Acid Production, and Suppressing Renal Inflammation.

Cisplatin-induced nephrotoxicity is associated with gut microbiota disturbance. The present study aimed to investigate whether supplementation of Lactobacillus reuteri and Clostridium butyricum (LCs) had a protective effect on cisplatin-induced nephrotoxicity through reconstruction of gut microbiota. Wistar rats were given different treatments: control, cisplatin (Cis), cisplatin + C. butyricum and L. reuteri (Cis+LCs), and C. butyricum and L. reuteri (LCs). We observed that cisplatin-treated rats supplemented with LCs exhibited significantly decreased renal inflammation (KIM-1, F4/80, and MPO), oxidative stress, fibrosis (collagen IV, fibronectin, and a-SMA), apoptosis, concentration of blood endotoxin and indoxyl sulfate, and increased fecal butyric acid production compared with those without supplementation. In addition, LCs improved the cisplatin-induced microbiome dysbiosis by maintaining a healthy gut microbiota structure and diversity; depleting Escherichia-Shigella and the Enterobacteriaceae family; and enriching probiotic Bifidobacterium, Ruminococcaceae, Ruminiclostridium_9, and Oscillibacter. Moreover, the LCs intervention alleviated the cisplatin-induced intestinal epithelial barrier impairment. This study indicated LCs probiotic serves as a mediator of the gut-kidney axis in cisplatin-induced nephrotoxicity to restore the intestinal microbiota composition, thereby suppressing uremic toxin production and enhancing butyrate production. Furthermore, the renoprotective effect of LCs is partially mediated by increasing the anti-inflammatory effects and maintaining the integrity of the intestinal barrier.

Astragalin Attenuates Dextran Sulfate Sodium (DSS)-Induced Acute Experimental Colitis by Alleviating Gut Microbiota Dysbiosis and Inhibiting NF-κB Activation in Mice.

With the ulcerative colitis (UC) incidence increasing worldwide, it is of great importance to prevent and treat UC. However, efficient treatment options for UC are relatively limited. Due to the potentially serious adverse effects of existing drugs, there is an increasing demand for alternative candidate resources derived from natural and functional foods. Astragalin (AG) is a type of anti-inflammatory flavonoid, with Moringa oleifera and Cassia alata being its main sources. In this study, we investigated the therapeutic effects of AG on mice with dextran sulfate sodium (DSS)-induced colitis. Our results suggested that AG treatment reduced weight loss and the disease activity index (DAI), prevented colon shortening and alleviated colonic tissue damage. AG treatment reduced the expression of pro-inflammatory cytokines and related mRNAs (such as TNF-α, IL-6, and IL-1ß), inhibited colonic infiltration by macrophages and neutrophils, ameliorated metabolic endotoxemia, and improved intestinal mucosal barrier function (increased expression levels of mRNAs such as ZO-1, occludin, and Muc2). Western blot analysis revealed that AG downregulated the NF-κB signaling pathway. Moreover, AG treatment partially reversed the alterations in the gut microbiota in colitis mice, mainly by increasing the abundance of potentially beneficial bacteria (such as Ruminococcaceae) and decreasing the abundance of potentially harmful bacteria (such as Escherichia-Shigella). Ruminococcaceae and Enterobacteriaceae (Escherichia-Shigella) were thought to be the key groups affected by AG to improve UC. Therefore, AG might exert a good anti-UC effect through microbiota/LPS/TLR4/NF-kB-related pathways in mice. The results of this study reveal the anti-inflammatory effect and mechanism of AG and provide an important reference for studying the mechanisms of natural flavonoids involved in preventing inflammation-driven diseases.